12 months, and then all subjects receive treatment on a 12-monthopen-label continuation. Three subjects have enrolled with onesubject completing the first six months of treatments and evalua-tions. This subject is a 51 year old male with Scheie syndrome whohas received five IT ERT injections without serious adverse events.Adverse events possibly related to IT ERT include low back pain, neckstiffness, and transient blurry vision. Cerebrospinal fluid (CSF)leukocytosis has not occurred. Opening pressure of CSF and CSFprotein have been borderline elevated from 20 to 25 cm H2O and 46to 50 mg/dL, respectively. Further study is needed to determinewhether IT ERT can be used to treat cognitive decline in MPS Ipatients who do not qualify for and/or are unable to havehematopoietic stem cell transplantation.

doi:10.1016/j.ymgme.2010.11.035

Basis for the relationship between Gaucher disease andsynucleinopathies

Seng Cheng, Pablo Sardi, Lamya Shihabuddin, Genzyme Corporation,Framingham, MA, USA

Mutations in the gene encoding glucocerebrosidase (GBA) resultin Gaucher disease (GD). Emerging evidence suggests that mutationsin GBA increase the risk factor for synucleinopathies, such asParkinson's disease (PD) and dementia with Lewy bodies (DLB).Parkinsonian manifestations have been noted in patients with GD andGBA mutations have been observed with increased frequency inpatients with sporadic PD or DLB. Lewy body-like α-synucleininclusions, a neuropathological hallmark of PD, have also been foundin patients with GD. To better understand the relationship betweenmutant GBA and α-synuclein accumulation, the behavior and brainhistopathology of two mouse models of GD were examined. Incontrast to age-matched wild type mice, both GBAD409V/D409V andGBAD409V/+ Gaucher mice showed progressive accumulation ofubiquitin aggregates in neurons starting at 6 months of age. Theubiquitin aggregates were co-localized with α-synuclein, similar tothose reported for Lewy neurites in PD and DLB. HomozygousGBAD409V/D409V mice also exhibited hippocampal memory deficitsin a novel object recognition behavioral test. Hence, the GBAD409V/D409V model of Gaucher disease would appear to recapitulate somefeatures of synucleinopathies. Interestingly, heterozygous GBA+/−mice did not display accumulation of ubiquitin aggregates suggestingthat the presence of a mutant GBA allele is required for thisphenotype. Moreover, memory impairment was only apparent inGaucher mice that retained less than 20% of normal GBA activity.Together, our results indicate that the presence of a D409V mutantallele and/or a decrease in GBA activity contribute to the observed α-synuclein pathology.

doi:10.1016/j.ymgme.2010.11.036

The use of saposin C and phosphatidylserine in functional studiesof glucocerebrosidase

Jae Choia, OmidMotabarb,Wei Zhengb, JuanMaruganb, Ellen Sidranskya,Ehud Goldina, aNational Human Genome Research Institute/NationalInstitutes of Health, Bethesda, MD, USA, bNIH Chemical Genomics Center,Rockville, USA

Glucocerebrosidase activity is deficient in patients with Gaucherdisease. Over the years, the diagnosis of this disease has been

performed by determining the enzyme activity in patient samples,most often using fibroblasts or lymphocytes. These preparations areincubated with labeled substrate and the amount of product ismeasured. Early on, it was discovered that the addition of sodiumtaurocholate could substitute for the natural activator of the enzyme,saposin C, providing the basis for a reliable and consistent diagnosticmethod. However, this procedure may not be sufficient for biochem-ical studies of the function of glucocerebrosidase, particularly in adrug discovery setting. In the process of validating our drug leads, wediscovered that the pH optimum of recombinant glucocerebrosidaseis abnormally high (5.9 for the wild-type enzyme and 7.2 for theN370S mutant enzyme). However, in the presence of saposin C andphosphatidylserine the pH optimum of both enzymes shifted to 4.9,which is the normal lysosomal pH. Furthermore, the enzymaticactivity of spleen homogenate and recombinant enzyme preparationscontaining saposin C and phosphatidylserine behaved similarly whentested against specific small compounds initially discovered from ascreen using the spleen homogenate. We conclude that saposin C is anecessary component for accurate assessment of functional activity ofglucocerebrosidase. This finding has relevance when testing for othernatural and pharmacological factors that modify the function of thisenzyme.

doi:10.1016/j.ymgme.2010.11.037

Feasibility and reliability of telemedicine administration of theUnified Batten Disease Rating Scale

Jennifer Cialone, Erika F. Augustin, Nicole J. Newhouse, Amy Vierhile,Frederick J. Marshall, Jonathan W. Mink, University of Rochester,Rochester, NY, USA

Introduction: Juvenile neuronal ceroid lipofuscionosis (JNCL;CLN3 disease; Batten disease) is an autosomal recessive neurode-generative disease of childhood characterized by vision loss,seizures, dementia, behavioral difficulties, and motor impairment.Symptoms typically begin around age 5 years; progression results insevere disability then death in the late 2nd or 3rd decade of life. Toquantify disease progression, we developed a valid and reliableclinical rating instrument, the Unified Batten Disease Rating Scale(UBDRS). The UBDRS also has potential to be a useful outcomemeasure for clinical trials. In its current form, the UBDRS requires in-person evaluation, often requiring subjects to travel long distances toparticipate in research studies. Thus, we sought to test the feasibilityand reliability of administration with remote video evaluation(telemedicine).

Methods: Subjects were evaluated at the University of Rochester orat the 2010 annual Batten Disease Support and Research Associationconference. A non-physician examiner directed administration of theUBDRS physical subscale while a trained neurologist rater completedthe rating by viewing a live video feed. Immediately preceding orfollowing the telemedicine evaluation, a second trained neurologistrater conducted an in-person rating. Reliability was determined byIntraclass Correlation Coefficient (ICC).

Results: To date, we have evaluated 8 subjects in the mannerdescribed. For the physical subscale score, the ICC was 0.9457,indicating excellent reliability. Ease of administration and subjectparticipation confirmed the feasibility of this approach.

Conclusions: Telemedicine administration of the UBDRS is feasibleand reliable. This supports the use of telemedicine evaluation infuture clinical trials.

doi:10.1016/j.ymgme.2010.11.038

Abstracts / Molecular Genetics and Metabolism 102 (2011) S3–S47 S11